Method and apparatus for the production of lead 212 for medical use

Abstract

The invention relates to a method for preparing lead (212) for medical use. This method comprises the production of lead (212) by the decay of radium (224) in a generator comprising a solid medium to which the radium (224) is bound, followed by the extraction of the lead (212) from the generator in the form of an aqueous solution A1, characterized in that the lead (212) contained in the aqueous solution A1 is purified from the radiological and chemical impurities, also contained in said aqueous solution, by a liquid chromatography on a column. The invention also relates to an apparatus specially designed for automated implementation in a closed system of said method. It further relates to lead (212) produced by means of this method and this apparatus. Applications: manufacture of radiopharmaceuticals based on lead (212), useful in nuclear medicine for the treatment of cancers, particularly by a-radioimmunotherapy, or for medical imaging, in both humans and animals.

The invention claimed is: 
     
       1. A method for producing an aqueous solution of lead-212, comprising:
 (a) producing lead-212 by decay of radium-224 in a generator comprising a cation-exchange resin, wherein the radium-224 is bound to the resin; 
 (b) eluting the lead-212 from the resin with a first aqueous solution comprising from 1.5 mol/L to 2.5 mol/L of a strong acid to form a second aqueous solution comprising the lead-212 and radiological and chemical impurities; 
 (c) purifying the lead-212 from the radiological and chemical impurities by liquid chromatography on a column, the column comprising a stationary phase comprising 4,4′(5′)-di-tert-butylcyclohexano-18-crown-6 in solution in an organic diluent not miscible with water, the liquid chromatography purification comprising:
 contacting the stationary phase with the second aqueous solution; 
 washing the stationary phase with a third aqueous solution comprising from 0.1 mol/L to 0.5 mol/L of a strong acid; and 
 eluting the lead-212 from the stationary phase with a fourth aqueous solution having a pH from 5 to 9 to form a fifth aqueous solution comprising the lead-212; and 
 
 (d) submitting the fifth aqueous solution to a bacteriological purification to prepare the aqueous solution of lead-212. 
 
     
     
       2. The method of  claim 1 , wherein the first and third aqueous solutions are hydrochloric acid or nitric acid solutions. 
     
     
       3. The method of  claim 1 , wherein the fourth aqueous solution is an ammonium acetate solution. 
     
     
       4. The method of  claim 3 , wherein the fourth aqueous solution comprises from 0.15 mol/L to 1 mol/L of ammonium acetate. 
     
     
       5. The method of  claim 1 , wherein the bacteriological purification comprises circulating the fifth aqueous solution through a bacteriological filter. 
     
     
       6. The method of  claim 1 , further comprising collecting the aqueous solution of lead-212. 
     
     
       7. The method of  claim 1 , wherein the aqueous solution of lead-212 comprises less than 11 ppb of lead other than lead-212, less than 2 ppb of vanadium, manganese, cobalt, copper, molybdenum, cadmium, tungsten and mercury, less than 20 ppb of iron, and less than 50 ppb of zinc. 
     
     
       8. A method for producing an aqueous solution of lead-212 in an automated manner, comprising the steps of:
 (a) producing lead-212 by decay of radium-224 in a generator comprising a cation-exchange resin and wherein the radium-224 is bound to the resin; 
 (b) eluting the lead-212 from the resin with a first aqueous solution comprising from 1.5 mol/L to 2.5 mol/L of a strong acid to form a second aqueous solution comprising the lead-212 and radiological and chemical impurities, the elution comprising drawing the first aqueous solution from a first solution source and injecting the first aqueous solution into the generator by a first pump; 
 (c) purifying the lead-212 from the radiological and chemical impurities by liquid chromatography on a column, the column comprising a stationary phase comprising 4,4′(5′)-di-tert-butylcyclohexano-18-crown-6 in solution in an organic diluent not miscible with water, and the liquid chromatography purification comprising:
 contacting the stationary phase with the second aqueous solution, the contacting comprising a circulation of the second aqueous solution from the generator to the column by means for connecting the generator with the column; 
 washing the stationary phase with a third aqueous solution comprising from 0.1 mol/L to 0.5 mol/L of a strong acid, the washing comprising drawing the third aqueous solution from a second solution source and injecting the third aqueous solution into the column by the first pump; and 
 eluting the lead-212 from the stationary phase with a fourth aqueous solution having a pH from 5 to 9 to form a fifth aqueous solution comprising the lead-212, the elution comprising drawing the fourth aqueous solution from a third solution source and injecting the fourth aqueous solution into the column by the first pump; 
 
 (d) submitting the fifth aqueous solution to a bacteriological purification to prepare the aqueous solution of lead-212, the bacteriological purification comprising a circulation of the fifth aqueous solution from the column to a bacteriological purification filter by means for connecting the column with the bacteriological purification filter; and 
 (e) collecting the aqueous solution of lead-212 in a flask, the collection comprising a circulation of the aqueous solution of lead-212 from the bacteriological purification filter to the flask by means for connecting the bacteriological purification filter with the flask; 
 
       wherein the first and second pumps, the means for connecting the generator with the column, the means for connecting the column with the bacteriological purification filter, and the means for connecting the bacteriological purification filter with the flask are commanded by an electronic processor. 
     
     
       9. The method of  claim 8 , wherein the first and third aqueous solutions are hydrochloric acid or nitric acid solutions. 
     
     
       10. The method of  claim 8 , wherein the fourth aqueous solution is an ammonium acetate solution. 
     
     
       11. The method of  claim 10 , wherein the fourth aqueous solution comprises from 0.15 mol/L to 1 mol/L of ammonium acetate. 
     
     
       12. The method of  claim 8 , wherein the aqueous solution of lead-212 comprises less than 11 ppb of lead other than lead-212, less than 2 ppb of vanadium, manganese, cobalt, copper, molybdenum, cadmium, tungsten and mercury, less than 20 ppb of iron, and less than 50 ppb of zinc.